1. Chronic Inflammation Permanently Reshapes Tissue-Resident Immunity in Celiac Disease
- Author
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Peter H.R. Green, Cezary Ciszewski, Bana Jabri, Dustin G. Shaw, Ian Lawrence, Vinod Kumar, Carol E. Semrad, Herman Gudjonson, Hilary Jericho, Jamie Rossjohn, Toufic Mayassi, Ranjana Gokhale, Mai T. Tran, Hoda E. Sayegh, Aaron R. Dinner, Jean-Christophe Grenier, Sonia S. Kupfer, Vincent van Unen, James E. McLaren, Kristin Ladell, Cisca Wijmenga, Matthew Dimaano, David Price, Jagoda Rokicka, Stefano Guandalini, Luis B. Barreiro, Hugh H. Reid, and Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI)
- Subjects
Glutens ,IMPACT ,Cell ,lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ,Receptors, Antigen, T-Cell ,Inflammation ,chemical and pharmacologic phenomena ,Disease ,Biology ,LYMPHOCYTES ,digestive system ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Diet, Gluten-Free ,MOLECULES ,0302 clinical medicine ,T(H)1 ,Immunity ,REGRESSION ,medicine ,Humans ,Antigens ,Intestinal Mucosa ,Intraepithelial Lymphocytes ,030304 developmental biology ,0303 health sciences ,Butyrophilins ,T-CELL-RECEPTOR ,T-cell receptor ,fungi ,MEMORY ,Receptors, Antigen, T-Cell, gamma-delta ,Immune surveillance ,Cytolysis ,Celiac Disease ,medicine.anatomical_structure ,HEK293 Cells ,Immunology ,Chronic Disease ,Intraepithelial lymphocyte ,POPULATIONS ,medicine.symptom ,030217 neurology & neurosurgery ,CD4(+) ,RESPONSES - Abstract
Contains fulltext : 215586.pdf (Publisher’s version ) (Open Access) Tissue-resident lymphocytes play a key role in immune surveillance, but it remains unclear how these inherently stable cell populations respond to chronic inflammation. In the setting of celiac disease (CeD), where exposure to dietary antigen can be controlled, gluten-induced inflammation triggered a profound depletion of naturally occurring Vgamma4(+)/Vdelta1(+) intraepithelial lymphocytes (IELs) with innate cytolytic properties and specificity for the butyrophilin-like (BTNL) molecules BTNL3/BTNL8. Creation of a new niche with reduced expression of BTNL8 and loss of Vgamma4(+)/Vdelta1(+) IELs was accompanied by the expansion of gluten-sensitive, interferon-gamma-producing Vdelta1(+) IELs bearing T cell receptors (TCRs) with a shared non-germline-encoded motif that failed to recognize BTNL3/BTNL8. Exclusion of dietary gluten restored BTNL8 expression but was insufficient to reconstitute the physiological Vgamma4(+)/Vdelta1(+) subset among TCRgammadelta(+) IELs. Collectively, these data show that chronic inflammation permanently reconfigures the tissue-resident TCRgammadelta(+) IEL compartment in CeD. VIDEO ABSTRACT.
- Published
- 2019